Diethylene glycol monoethyl ether is used as a solvent in a wide variety of manufacturing processes. The commercial grade typically contains from about 1,000 parts per million (hereinafter "ppm") by weight to about 2,000 ppm by weight ethylene glycol as an impurity. The presence of this amount of ethylene glycol, which is toxic when ingested, renders the commercial grade of diethylene glycol monoethyl ether unusable as a solvent in pharmaceutical manufacturing applications. In order to be suitable for use in pharmaceutical manufacturing applications, the ethylene glycol content of diethylene glycol monoethyl ether must be reduced to less than about 25 ppm by weight.
Removing ethylene glycol, which has a boiling point of 197.2.degree. C. (Hawley's Condensed Chemical Dictionary, 13th Ed., 1997), from diethylene glycol monoethyl ether using conventional distillation equipment is difficult and inefficient because diethylene glycol monoethyl ether has an overlapping boiling point range of 195-202.degree. C. (Hawley's Condensed Chemical Dictionary, 13th Ed., 1997). Thus, the yield of pharmaceutical grade diethylene glycol monoethyl ether using conventional distillation equipment is quite low. A method which would permit the effective and economic removal of ethylene glycol from diethylene glycol monoethyl ether is therefore highly desired.
Azeotropic distillation is a well-known means of separating two compounds having boiling points in close proximity. In a typical azeotropic distillation, a third compound which forms an azeotrope with only one of the closely boiling components is added to form a mixture, the mixture is subjected to distillation, and the azeotrope is removed as an overhead product thereby effecting separation of the compounds having close boiling points. Ideally, the azeotrope-forming agent, which is sometimes referred to as an entrainer, is separated from the component with which it forms the azeotrope by conventionally known means, such as by phase separation, and returned to the distillation apparatus for reuse.
Each closely boiling binary system presents its own special problems so as to render past experience of little value and future results unpredictable. Thus, the selection of an azeotrope-forming agent is seldom a simple task. Not only must an azeotrope-forming agent form an azeotrope with only one of the closely boiling components having the proper volatility, the components of the azeotrope must also be capable of being easily separated in highly pure form for reuse in the process or for recovery as a final saleable, useful product. Moreover, the azeotrope-forming agent preferably should be relatively inexpensive, nontoxic, nonreactive, and noncorrosive.